Cardiovascular & Haematological Disorders - Drug Targets - Volume 19, Issue 2, 2019

Objective: Clonidine is a centrally acting antihypertensive drug. Hypotensive effect of clonidine is mediated mainly by central α2-adrenoceptors and/or imidazoline receptors located in a complex network of the brainstem. Unfortunately, clonidine produces side effects such as sedation, mouth dry, and depression. Moxonidine and rilmenidine, compounds of the second generation of imidazoline drugs, with fewer side effects, display a higher affinity for the imidazoline receptors compared with α2-adrenoceptors. The antihypertensive action of these drugs is due to inhibition of the sympathetic outflow primarily through central I1-imidazoline receptors in the RVLM, although others anatomical sites and mechanisms/receptors are involved. Agmatine is regarded as the endogenous ligand for imidazoline receptors. This amine modulates the cardiovascular function. Indeed, when administered in the RVLM mimics the hypotension of clonidine. Results: Recent findings have shown that imidazoline drugs also exert biological response directly on the cardiovascular tissues, which can contribute to their antihypertensive response. Currently, new imidazoline receptors ligands are in development. Conclusion: In the present review, we provide a brief update on the cardiovascular effects of clonidine, moxonidine, rilmenidine, and the novel imidazoline agents since representing an important therapeutic target for some cardiovascular diseases.

Adenosine, a purine nucleoside, is produced broadly and implicated in the homeostasis of many cells and tissues. It signals predominantly via 4 purinergic adenosine receptors (ADORs) – ADORA1, ADORA2A, ADORA2B and ADORA3 in addition to non-ADOR mediated effects. Through these signaling mechanisms, adenosine exerts effects on numerous cell types crucial to maintaining vascular homeostasis, especially following vascular injury. Both in vitro and in vivo models have provided considerable insights into adenosine signaling and identified targets for therapeutic intervention. Numerous pharmacologic agents have been developed that modulate adenosine signaling, both through design as specific ADOR agonists and antagonists and as offtarget effects of existing anti-platelet medications. Despite this, adenosine has yet to be firmly established as either a therapeutic or a prognostic tool in clinical medicine to date. Herein, we provide a bench-to-bedside review of adenosine biology, highlighting the key considerations for further translational development of this promising molecule.

Development of cardiomyopathy (CM) is dependent upon several factors. However, the reaction of the immune response against myocardial tissue due to microbial and viral infections plays an important role in this disease. Therefore, the purpose of this study is to investigate the relationship between HLAs and their pathogenic mechanisms in the incidence of CM. Relevant literature was identified by a PubMed search (1989-2017) of English-language papers using the terms “Cardiomyopathy”, “Human leukocyte antigen or HLA”, “immune response”, and “polymorphism”. If CM patients are afflicted with viral and microbial infections, HLA class II molecules, which are not expressed on myocardial tissue in normal conditions, are mainly expressed on it. As a result, these HLAs present self- antigens and provoke autoimmune responses against myocardial tissue. On the other hand, the occurrence of polymorphism as well as disrupted expression of miRNAs can affect HLA expression, leading to hypertrophy and fibrosis of cardiac muscle. Finally, it is inferred that the expression evaluation of HLAs as well as identification of polymorphisms in their coding genes can be effective diagnostic factors in the detection of people susceptible to CM.

Vitamin D, a steroid hormone is primarily known for its role in calcium and bone mineral homeostasis. Over the years, vitamin D has been implicated in various non-skeletal diseases. The extraskeletal phenomenon can be attributed to the presence of vitamin D receptors (VDRs) in almost all cells and identification of 1-α hydroxylase in extrarenal tissues. The vitamin D deficiency (VDD) pandemic was globally reported with increasing evidence and paralleled the prevalence of diabetes, obesity and cardiovascular diseases (CVDs). A dependent link was proposed between hypovitaminosis D glycemic status, insulin resistance and also the other major factors associated with type 2 diabetes leading to CVDs. Insulin resistance plays a central role in both type 2 diabetes and insulin resistance syndrome. These 2 disorders are associated with distinct etiologies including hypertension, atherogenic dyslipidemia, and significant vascular abnormalities that could lead to endothelial dysfunction. Evidence from randomised clinical trials and meta-analysis, however, yielded conflicting results. This review summarizes the role of vitamin D in the regulation of glucose homeostasis with an emphasis on insulin resistance, blood pressure, dyslipidaemia, endothelial dysfunction and related cardiovascular diseases and also underline the plausible mechanisms for all the documented effects.

Background: There has been considerable interest in the potential health benefits of borage. Little information is available regarding the safety of this plant. The purpose of this study was to evaluate the impact of borage on the mouse heart. Methods: Different amounts of borage extract were injected in mice. The mice were randomly divided into 4 groups including group1 (Control group without injection), group2, 3 and 4 that received 12.5 mg/kg, 25 mg/kg and 50 mg/kg respectively for 28 days. Oxidative stress parameters (lipid peroxidation, total glutathione groups assay and cupric assay) and biochemical (Creatine kinase activity and total cholesterol) and hematology parameters were evaluated. Furthermore, histopathology study was carried out on heart tissues. Results: We found that there was no significant difference in oxidative stress parameters and biochemical parameters between the control group and the groups that received different amounts of borage extract. There were also no changes in histopathology study. In blood parameters, the level of erythrocytes, hematocrit and hemoglobin decreased to 50mg/kg, whereas the level of MCH and MCV decreased in high doses. Conclusion: This article suggested that borage did not cause significant damage to the heart tissue in mice model. In hematology factors, significant changes were observed in erythrocytes and related parameters. Therefore, hematotoxicity of consumption this plant should be considered at high doses.

Aims: To examine if pentraxin can help identify patients benefitting most from primary Percutaneous Coronary Intervention (PCI) vs. fibrinolysis. Methods: Patients with acute ST-Elevation Myocardial Infarction (STEMI) were consecutively recruited from a community center without PCI and a tertiary center with PCI facilities. Left ventricular ejection fraction (LVEF) was determined echocardiographically at baseline and 5 days after the index admission; the difference between two measurements was considered as the magnitude of improvement. We used regression models to test the hypothesis that the magnitude of the advantage of PCI over fibrinolysis in preserving LVEF 5 days after STEMI is modified by pentraxin 3 (PTX3). Results: The functional advantage (LVEF) of the PCI over fibrinolysis has been determined by PTX3. LVEF was attenuated and even reversed as PTX3 level increased. The primary PCI of the participants with less than 7 ng.ml-1 PTX3 level, achieved a clinically significant increase in the LVEF as compared to fibrinolysis. At lower levels of PTX3, PCI shows a conspicuous advantage over fibrinolysis in terms of the probability of developing an LVEF <40%. Conclusion: We demonstrated not only the functional advantage of PCI over fibrinolysis performed within the recommended time frames but also the relative advantage of its relevance to the baseline PTX3 levels. PTX3 can play a role in determining the choice of best therapy. More than 75% of patients with STEMI who have PTX3 levels ≤7 ng.ml-1 imply the need of PCI.

Background: Investigation of rare bleeding disorders in Latin-America. Objectives: The report of a new case of FX deficiency due to a compound heterozygosis. Methods: Accepted clotting procedures were used. Sequencing of DNA was carried out by means of Applied Biosystems Instruments. Results: A compound heterozygote due to the association of a new mutation (Gla72Asp) with an already known mutation (Gly154Arg) of the FX gene is reported. The proposita is a 38 year old female who had a moderate bleeding tendency (menorrhagia, epistaxis, easy bruising). The proposita has never received substitution therapy but in the occasion of a uterine biopsy. The mother was asymptomatic but was a heterozygote for the new mutation. The father was asymptomatic but had deserted the family and could not be investigated. After this abandonment the mother of the proposita re-married with an asymptomatic man and she gave birth to a son who was asymptomatic but was also heterozygous for the new mutation (Gla72Asp). As a consequence it has to be assumed that the first husband of the mother of the proposita was heterozygous for the known mutation (Gly154Arg). Conclusions: This is the third case of a new mutation in the FX gene reported, during the past few years, in Argentina.